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Many developing countries including Ghana are currently experiencing dual disease burdens emerging from an unprecedented risk overlap that drive their epidemiological transitions. Yet, siloed and disintegrated approaches continue to take precedence in health research and policy programs that drive competition for limited resources to address competing health problems. The objective of this study was to offer empirical evidence in support of a cogent argument for an integrated framework for the study and management of infectious and chronic health conditions in Ghana. We did so by examining the prevalence, determinants, and neighborhoods trajectories of the double burden of disease using data from a cross-sectional neighborhood-based study in Ghana. We fitted multinomial multilevel multivariate models to a sample of 1377 individual surveys and the results presented as odds ratios. Findings show that amidst a rising burden of NCDs, infectious diseases remain the most common health condition and participants in deprived neighborhoods were significantly more likely to report poor health outcomes. Risk factors such as tobacco and alcohol consumption were significantly associated with NCDs and infectious diseases and respondents who reported being diagnosed with NCDs and infectious diseases in the past year were likely to engage in leisure time physical activities and eat healthy. Based on our findings, we recommend health reforms in Ghana and argue for the design and implementation of an integrated framework for the study and management of the double burden of disease in Ghana and similar developing country settings.